Project Summary/Abstract: The goal of this proposal is to develop and test a combined quasi-static compression and shear wave ultrasound elastography system to image the linear and nonlinear mechanical properties of breast tissues with high spatial resolution. There is strong evidence that non-linear mechanical properties, e.g. nonlinear shear modulus and strain dependent shear wave velocity, can help to differentiate malignant and benign lesions of the breast. Furthermore, tissues with distinct non-linear mechanical properties can exhibit similar small-strain properties and lack contrast in conventional shear wave elastography. The proposed system addresses this limitation and will exploit non-linear mechanical properties to provide an additional feature for lesion classification. We propose to construct and test a system using a combination of quasi-static strain and ARFI- based shear wave elastography to measure the strain dependent shear wave velocity of breast tissue. A range of static ?prestrains? will be applied to the tissue while ARFI-induced shear wave velocity is estimated. By combining these shear wave speed measurements with speckle tracking to estimate local strain, we will measure the strain dependence of shear wave velocity of tissues. We will validate the system with non-linear tissue mimicking phantoms, and collect pilot data on strain dependence of shear wave velocity in mastectomy and in-vivo breast tissues. Recent state mandates to inform women with dense breasts of the potential insensitivity of mammography have resulted in increased ultrasound screening. This screening finds additional cancers, but also many more false positives. High resolution imaging of non-linear mechanical properties could improve the positive predictive value of ultrasound and allow more patients to be followed rather than biopsied, leading to significant reductions in health care costs.